The OCRL gene product is only one of many enzymes implicated in the metabolism of phosphatidylinositols (PIs). The lab is beginning a systematic effort to isolate and delete the genes encoding enzymes in PI metabolism in order to understand what the different enzymes and different isoforms of these enzymes are doing physiologically in the cell. Mice lacking the alpha-isoform of phosphatidylinositol (4,5) 3-kinase have been generated and found to undergo spontaneous embryonic demise at days 9.5-10.5 post coitum. The embryos are small and appear to be deficient in their response to growth factors. Embryonal stem cells lacking the beta isoform have been generated and chimeric mice carrying the ES cells have been born. We are currently waiting for the chimeric mice to reach maturity to being breeding to see if we have germ-line transmission of the ES cells.